Candidiasis (yeast infection or thrush) is a fungal infection (mycosis) caused by a member of the Candida species. Candida yeasts are usually present in most people, but their uncontrolled multiplication can result in infection of the mouth, skin or vagina. The overgrowth of Candida yeasts is kept in check by other naturally occurring microorganisms, e.g. bacteria co-existing with the yeasts in the same locations, and by the human immune system. One of the common causes of candidiasis may be the frequent use of antibiotics that are clinically expected to destroy harmful and disease causing microorganisms in the body, but they may also destroy the beneficial microorganisms which are responsible for keeping the growth of yeasts (fungi) in check. The destruction of beneficial microorganisms may cause the yeasts (fungi) to grow out of control resulting in condition known as candidiasis moniliasis, or a “yeast” infection. A weakened or undeveloped immune system or metabolic disorders, such as diabetes may also predispose individuals to Candidiasis.
Oral candidiasis (oral thrush) is the most common fungal infection in the mucous membranes of the mouth. Although oral thrush can affect anyone but it is more prevalent in babies and toddlers, people who wear dentures, and in people with compromised immune systems, especially those suffering from acquired immune deficiency syndrome (AIDS), cancer patients undergoing chemotherapy and those who have undergone bone marrow transplantation or solid organ transplantation or other immunocompromised patients. As indicated herein above, the disease causing pathogen is usually Candida species (fungi). Most commonly, oral candidiasis is caused by Candida albicans (C. albicans), however, the emergence of other species of Candida causing oral candidiasis have been reported. In a relatively recent report of 153 HIV-positive patients, it was described that 21% of the patients had oral candidiasis caused due to non-Candida albicans species, the most common of which was Candida glabrata (Masia Canuto et al.; Med. Clin. 112:211-214, (1999)). Similarly, it was also found that 25% of the yeast species isolated from persons with AIDS were non-Candida albicans species (Morace G. et al; Eur. J. Epidemiol. 6:398-403(1990)). In a most recent study involving detection and identification of Candida species responsible for causing oral candidiasis in children and adolescents having cancer, it was found that although C. albicans was the most common species, other species namely Candida parapsilosis (C. parapsilosis), Candida tropicalis (C. tropicalis), Candida krusei (C. krusei), Candida glabrata (C. glabrata) and Candida lusitaniae (C. lusitaniae) were also responsible for causing oral candidiasis (Med. Oral. Patol. Oral. Cir. Bucal; 2007 Oct. 1; 12(6); E419-23 (2007). The most common symptoms of oral candidiasis are discomfort and burning of the mouth and throat and an altered sense of taste. Oral candidiasis is characterised by the appearance of whitish velvety plaques on the mucous membrane of the mouth and tongue, and scraping of this whitish material reveals a red (erythematous) rash underneath with pinpoint bleeding. In immunocompromised people, the infection may be massive and in addition it may spread to the esophagus producing candidal esophagitis causing pain in the mouth and eventually resulting in painful difficult swallowing.
The standard therapy for the treatment of oral candidiasis involves use of antifungal agents selected from polyene derivatives such as amphotericin B and the structurally related compound, nystatin (mycostatin); and the azole antifungal agents such as miconazole, ketaconazole, fluconazole, itraconazole or clotriamazole. However, there are limitations to the use of these synthetic antifungal agents in terms of their poor safety profile, multiple drug-drug interactions, excessive cost and lack of efficacy due to the growing resistance of Candida species to the conventional antifungal agents.
The prevalence of resistance of the Candida species, especially C. albicans isolated from patients with AIDS, to antifungal agents namely amphotericin B and fluconazole have been reported (Law D. et al., J. Antimicro. Chemo (1994) 34, 659-668). The evolution of resistance of candida species particularly the experimental population of C. albicans to azole antifungal agents, especially fluconazole, ketoconazole and itraconazole (Leah E. Cowen et al., J. Bacteriology, March 2000, 182 (6), p. 1515-1522) further renders the treatment less effective. Also, evidences indicate that fluconazole resistant C. albicans, can be a cause of recurrent oral candidiasis in patients with HIV infection, patients receiving cancer chemotherapy and patients who have undergone bone marrow transplantation or solid organ transplantation (Kieren A. Marr et al., Antimicrobial Agents and Chemotherapy, Oct. 1998; 42(10): 2584-2589).
Use of alternative therapies, particularly herbal-based therapies, is gaining momentum throughout the world. Several plants, plant extracts or substances derived from plants have been used for years to treat a wide range of diseases. The use of herbal compositions for the treatment of diseases of the oral cavity is known in the art and is gaining increased importance. Essential oils extracted from herbs have been provided for use in complementary medicine for bacterial and fungal infections. Japanese Patent Application no. 2003089652A relates to an herbal composition for preventing the onset of and for the treatment of oral candidiasis (oral thrush). The composition comprises of blends of various essential oils as active ingredients, which are selected from tea tree oil, Shinsei lavender oil, French lavender oil, spike lavender oil, the attar of rose, geranium oil, patchouli oil, lemon GURASU oil and palmarosa oil. The essential oil components are terpinene-4-ol, linalool, citranellol, geraniol, citral, citronellal and hinokitiol.
The plant, Piper cubeba L. (P. cubeba), commonly known as Kababchini (in India) belongs to Piperaceae family. The P. cubeba plant has been widely used in Asia as a condiment, food additive and a soothing agent for burning throat and for treating coughs. Use of the P. cubeba extract in combination with other plant extracts in the treatment of certain medical ailments is reported in the art. For instance, U.S. Published Patent Appln. No. 20040126441 A1 teaches a synergistic herbal composition comprising extracts of P. cubeba, Glycyrrhiza glabra, Acorus calamus Alpinia galanga, Zingiber officinale along with pharmaceutically acceptable additives for use as an anti-cough, anti-tussive, and throat soothing formulation. JP Published Patent Appln. No. 56083416A relates to a composition for oral cavity for preventing dental caries and pyorrhea alveolaris, wherein the composition comprises one or more materials extracted with organic solvents from plants selected from the group consisting of Ginkyo biloba L., Anethum graveolens L., Piper Cubeba L., Nardostachys jatamansi DC, Zingiber officinale Roscoe, Asiasarum Sieboldi F. Maekawa, Bupleurum Falcatum L., Malva silvestris L., Caesalpinia sappan L., Terminalia charbrila Rety, etc. Japanese Published Patent Appln No. 2001278800A relates to a cariostatic agent (anti-caries agent) containing at least one extract of a plant selected from Sariawan (Olygala glomerata Lour) or Kemukus (P. cubeba L) wherein the cariostatic agent is formulated as a composition for use as a mouthwash and also as an additive in food or a drink to prevent diseases of oral cavity, especially dental plaque. A study report (Silva M L et al., Phytotherapy Research, 2007, 21(5): 420-2) discloses activity of an ethanolic extract of P. cubeba against oral pathogens (microorganisms). The microorganisms used in the study included Enterococcus faecalis, Streptococcus salivarius, Streptococcus mitis, Streptococcus mutans, Streptococcus sobrinus, Streptococcus sanguinis and C. albicans. According to the report, the crude ethanolic extract from P. cubeba seeds, (−)-cubebin and its semi-synthetic derivatives exhibited activity against said microorganisms. The crude extract was found to be most active against Streptococcus salivarius. 
It is evident from the current art that there still exists a long felt need and a strong demand for an oral composition for the treatment of oral candidiasis, which can combat the adverse side effects associated with synthetic drugs, overcome the problem of resistance to conventional antifungal agents and also provide additional benefits. The present invention provides a solution to this problem in the form of an oral herbal composition which can fulfill the widely recognized need by providing an effective and safe treatment for oral candidiasis. The herbal composition also delivers other additional organoleptic benefits.